O2–081 - BRAF, PIK3CA Alterations can Predict Outcomes to Cetuximab Contained Conversion Chemotherapy in Wild-Type KRAS CLM

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Background: Our previous research accepted by JCO,2013, DOI:10.1200/JCO.2012.44.8308: Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients With KRAS Wild-Type Unresectable Colorectal Liver-Limited Metastases demonstrated cetuximab contained chemotherapy can efficiently converts the unresectable colorectal cancers live-limited metastasis(CLM) to resectable ones than chemotherapy alone. But until now the reported objective response rate(ORR) with Cetuximab contained chemotherapy to wild-type KRAS tumors ranged from 17% to 60% with metastasic colorectal cancers(mCRC). It is possible that other genetic mutations, constitutively activating the epidermal growth factor receptor (EGFR) pathway, are present in the non-responding wild-type KRAS patients. Methods: We retrospectively analyzed ORR, progression-free (PFS) and overall survival (OS) with respect to the mutational status of BRAF, PIK3CA and PTEN in 70 wild-type KRAS CLM patients treated with Cetuximab contained regimens as first-line therapy. DNA was extracted from primary lesions and the mutation of BRAF, PIK3CA and PTEN were detected by Pyrosequencing. Results In the 70 wild-type KRAS patients, with univariate analysis, BRAF (n = 5), PIK3CA (n = 7) and PTEN (n = 3) mutations were associated with ORR (p = 0.001, P = 0.020, P = 0.018 respectively) and shorter OS (p < 0.001, p < 0.001, p = 0.005 respectively), BRAF and PIK3CA mutations with worse PFS (p < 0.001, p = 0.033 respectively). With multivariate analysis, BRAF mutations were independently associated with worse PFS and OS (p < 0.001, p < 0.001 respectively), PIK3CA was independently associated with ORR (p = 0.037) and shorter OS (p < 0.001), PTEN mutation was not independently associated with ORR, PFS and OS. Conclusions: BRAF and PIK3CA could better predict the outcomes to cetuximab contained conversion chemotherapy in wild type KRAS CLM.